The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch ...and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation. Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that activates TRPV1 and whose pruritic activity, as well as that of histamine, occurs through the activation of this ion channel. These findings provide insights into the molecular basis of oleic acid inhibition of TRPV1 and also into a way of reducing the pathophysiological effects resulting from its activation.
The characterization of the molecular mechanisms, such as high light irradiance resistance, that allowed plant terrestralization is a cornerstone in evolutionary studies since the conquest of land by ...plants played a pivotal role in life evolution on Earth. Viridiplantae or the green lineage is divided into two clades, Chlorophyta and Streptophyta, that in turn splits into Embryophyta or land plants and Charophyta. Charophyta are used in evolutionary studies on plant terrestralization since they are generally accepted as the extant algal species most closely related to current land plants. In this study, we have chosen the facultative terrestrial early charophyte alga
to perform an integrative transcriptomic and metabolomic analysis under high light in order to unveil key mechanisms involved in the early steps of plants terrestralization. We found a fast chloroplast retrograde signaling possibly mediated by reactive oxygen species and the inositol polyphosphate 1-phosphatase (SAL1) and 3'-phosphoadenosine-5'-phosphate (PAP) pathways inducing gene expression and accumulation of specific metabolites. Systems used by both Chlorophyta and Embryophyta were activated such as the xanthophyll cycle with an accumulation of zeaxanthin and protein folding and repair mechanisms constituted by NADPH-dependent thioredoxin reductases, thioredoxin-disulfide reductases, and peroxiredoxins. Similarly, cyclic electron flow, specifically the pathway dependent on proton gradient regulation 5, was strongly activated under high light. We detected a simultaneous co-activation of the non-photochemical quenching mechanisms based on LHC-like stress related (LHCSR) protein and the photosystem II subunit S that are specific to Chlorophyta and Embryophyta, respectively. Exclusive Embryophyta systems for the synthesis, sensing, and response to the phytohormone auxin were also activated under high light in
leading to an increase in auxin content with the concomitant accumulation of amino acids such as tryptophan, histidine, and phenylalanine.
We aimed to identify presurgical and surgical risk factors for intraoperative complications in patients with pheochromocytomas. A retrospective study of patients with pheochromocytomas who underwent ...surgery in ten Spanish hospitals between 2011 and 2021 was performed. One hundred and sixty-two surgeries performed in 159 patients were included. The mean age was 51.6 ± 16.4 years old and 52.8% were women. Median tumour size was 40 mm (range 10–110). Laparoscopic adrenalectomy was performed in 148 patients and open adrenalectomy in 14 patients. Presurgical alpha- and beta-blockade was performed in 95.1% and 51.9% of the surgeries, respectively. 33.3% of the patients (n = 54) had one or more intraoperative complications. The most common complication was the hypertensive crisis in 21.0%, followed by prolonged hypotension in 20.0%, and hemodynamic instability in 10.5%. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more commonly than patients pre-treated with other antihypertensive drugs (51.1% vs 26.5%, P = 0.002). Intraoperative complications were more common in patients with higher levels of urine metanephrine (OR = 1.01 for each 100 μg/24 h, P = 0.026) and normetanephrine (OR = 1.00 for each 100 μg/24 h, P = 0.025), larger tumours (OR = 1.4 for each 10 mm, P < 0.001), presurgical blood pressure > 130/80 mmHg (OR = 2.25, P = 0.027), pre-treated with doxazosin (OR = 2.20, P = 0.023) and who had not received perioperative hydrocortisone (OR = 3.95, P = 0.008). In conclusion, intraoperative complications in pheochromocytoma surgery are common and can be potentially life-threatening. Higher metanephrine and normetanephrine levels, larger tumour size, insufficient blood pressure control before surgery, pre-treatment with doxazosin, and the lack of treatment with perioperative hydrocortisone are associated with higher risk of intraoperative complications.
The association between breast cancer (BCa) presence and altered glucose/insulin metabolism is controversial likely due to an inaccurate insulin resistance (IR) assessment and inappropriate ...stratification of patients by body-mass index (BMI) and menopausal state. 148 women with suspect of sporadic BCa were stratified by BMI and menopause. Fasting levels of glucose, insulin, glycohemoglobin and selected IR-related and tumor-derived markers were measured. Glucose/insulin levels during OGTT were used to calculate insulin resistance/sensitivity indexes. Analysis of 77 BCa-bearing patients and 71 controls showed an association between BCa and IR as demonstrated by impaired glucose/insulin homeostasis (increased fasting- and OGTT-induced glucose levels) and deteriorated IR indexes, which was especially patent in premenopausal women. The association between BCa presence and IR was markedly influenced by BMI, being obese BCa patients significantly more insulin resistant than controls. BCa presence was associated to elevated levels of IR (glucose, triglycerides) and tumor-derived (VEGF) markers, especially in overweight/obese patients. BCa presence is associated to IR in overweight/obese premenopausal but not in premenopausal normal weight or postmenopausal women. Our data support a bidirectional relationship between dysregulated/imbalanced glucose/insulin metabolism and BCa, as tumor- and IR-markers are correlated with the impairment of glucose/insulin metabolism in overweight/obese premenopausal BCa patients.
Abstract
The conservation and maintenance of earthen buildings is crucial, especially when dealing with heritage sites. This normally involves considerable effort in preliminary studies, which must ...be well planned in order to efficiently manage any restoration. This case study proposes a methodology to briefly assess the current state of a historical rammed-earth wall, to bring to light specific information regarding approaches for subsequent studies or decisions. This methodology is based on the study of damage and risk as a tool to swiftly discern critical areas or issues needing immediate attention. The procedure is illustrated on an outstanding heritage building: the Alcázar of King Don Pedro I in Carmona (Seville, Spain). Our conclusions confirm that this methodology constitutes an efficient and straightforward means to obtain not only a preliminary assessment of rammed-earth walls, but also objective and useful criteria for decision-makers.
The efficacy and safety of using high concentrations of oxygen during hypothermic machine perfusion (HMP) have not been fully elucidated to date. This study investigated the impact of administering ...high concentrations of oxygen on renal function during HMP in a porcine donation after circulatory death (DCD), as well as the metabolic and biochemical effects of this method. A randomized nonblinded cohort study was established in a porcine transplant (KT) model mimicking Maastricht type III DCD under oxygen-supplemented HMP (Ox-HMP) compared to non-supplemented (nOx-HMP) (LifePort® kidney transporter) conditions. The primary endpoint was evolution of renal function post-KT, whereas secondary endpoints included changes in perfusion dynamics, miRNA expression and cellular lesion measured by LDH and lactate levels in perfusate, lipid peroxidation in kidney biopsies, ATP generation, epithelial mesenchymal transition (EMT) and oxidative gene expression in cell cultures and histology evaluation. ATP generation and oxidative stress, as measured by lipid peroxidation, increased simultaneously after warm ischemia in the Ox-HMP group. Ox-HMP did not exhibit a significant effect on kidney function or animal survival. A significant increase in lipid peroxidation was observed in the Ox-HMP group. This resulted in a greater expression of the genes responsible for producing superoxide dismutase 1 (SOD-1) and catalase oxygenation enzymes, although only SOD-1 showed statistical significance. Respiratory chain dysfunction was maintained in the Ox-HMP group with a non-significant decrease in ATP production, increased proton leakage, and a decrease in respiratory reserve. Regarding epithelial-mesenchymal transition, an upward trend in the expression of vimentin, fibronectin, and collagen genes was observed only in the Ox-HMP group. Finally, the expression levels of miR-101 and miR-126, related to characteristic functions of the tubular epithelium, were significantly modified (miRNA levels expressed as DCT. A brief bubble Ox-HMP treatment did not show a clear positive effect on renal function and oxidative stress markers. The role and safety of adding oxygen during HMP still need to be elucidated. Currently, this Ox-HMP method cannot be considered standard practice.
Aunque la construcción con bloques de tierra (BT) está avalada por numerosos trabajos científicos, existe una desconfianza sobre su viabilidad constructiva, agravada por la falta de formación técnica ...específica. Ante esta incertidumbre, muy presente en el ámbito español, es preciso dar respuestas técnicas fundamentadas. En esa dirección, este artículo expone el diseño y validación de una herramienta para la evaluación de la viabilidad constructiva del BT. Con ese fin, se seleccionan 29 casos de estudio en España, con los que se establecen las determinaciones constructivas y los indicadores para la evaluación de un grado de idoneidad técnica. Este parámetro, como resultado de la herramienta propuesta, sirve como apoyo a la toma de decisiones, la mejora del diseño y la eficiencia de las soluciones que emplean BT. Se concluye con la validación de la herramienta que demuestra su fiabilidad y adaptabilidad a cualquier situación. Finalmente, a partir del análisis de casos, se expone cómo la calidad del producto unida a condiciones externas adversas, aún con diseños constructivos correctos, define una situación común por la que el grado de idoneidad de la solución es reducida. Por lo tanto, es necesario exigir también productos con avales y prescripciones que garanticen y ofrezcan suficiente seguridad técnica.
Objetivo: Conocer la producción científica existente sobre el estado actual de la hemodiálisis domiciliaria.
Material y Método: Se ha realizado una revisión integrativa mediante una búsqueda en las ...bases de datos Pubmed, Scopus y Google Académico. Se incluyeron artículos científicos originales y de revisión, en inglés y español, excluyendo aquellos artículos que no presentaban resultados o que no estuviesen en texto completo.
Resultados: Se han incluido 23 artículos publicados entre el año 2012 y 2017. La hemodiálisis domiciliaria es poco utilizada en el mundo, a excepción de Australia y Nueva Zelanda. Las series publicadas encuentran mejor supervivencia en los pacientes en hemodiálisis domiciliaria diaria o intensiva, respecto a otras modalidades de terapia sustitutiva renal, así como mejores resultados clínicos. Como principales ventajas de la técnica, se destaca la flexibilidad en la vida diaria y la independencia del centro sanitario. Como principal inconveniente se ha encontrado un aumento de las infecciones relacionadas con el uso de catéteres venosos centrales o la técnica de punción en “ojal”.
Conclusiones: La hemodiálisis domiciliaria presenta como principal ventaja la mayor libertad y flexibilidad para que el paciente dirija su propio tratamiento, siendo el principal inconveniente, una mayor probabilidad de padecer infecciones, relacionadas con el acceso vascular. Cuando se realiza hemodiálisis domiciliaria diaria o intensiva los resultados clínicos se muestran superiores a los otros procedimientos de diálisis, siendo comparables a los del trasplante renal. El papel de enfermería es fundamental en el desarrollo de esta técnica, especialmente en el proceso clave de la enseñanza al paciente y familiar.
Objetivo: El objetivo del presente estudio fue conocer el grado de conocimiento sobre el trasplante de vivo emparentado de los pacientes en hemodiálisis. Pacientes y Método: Se realizó un estudio ...observacional descriptivo y transversal, en 214 pacientes en hemodiálisis con una edad media 68.4±14.4 años (35% mujeres). El estudio se llevó a cabo en el Servicio de Nefrología del Hospital Reina Sofía de Córdoba. Se analizó el grado de conocimiento sobre el trasplante renal de vivo emparentado mediante entrevista con un cuestionario estructurado de elaboración propia. Resultados: El 21% de los pacientes estaban en lista de espera. El 96% de estos pacientes conocían la posibilidad del trasplante de donante vivo, mostrando una asociación estadísticamente significativa. El 83% de los que conocían el trasplante de vivo habían estado > 6 meses en la consulta de pre-diálisis, y el 56% de ellos había recibido la información del nefrólogo/enfermera. El 46% de los pacientes en lista de espera estarían dispuestos a aceptar un riñón de un familiar, el 53% de su pareja y el 46% de un amigo. Conclusiones: Los pacientes incluidos en lista de espera del Servicio de Nefrología de Córdoba están en su mayoría informados del trasplante de vivo emparentado, y todos, han sido informados en la consulta pre-diálisis o al inicio de diálisis, por el personal sanitario. Casi la mitad de todos los pacientes, incluidos los que no están en lista de espera, están dispuestos a aceptar un riñón de un familiar, de su pareja o de un amigo/a.
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